Responsiveness to bradykinin in veins of hypercholesterolemic humans

Hypercholesterolemia impairs endothelium-dependent dilation in arteries. We tested the hypothesis that hypercholesterolemia impairs endothelium-dependent vasodilation by an interaction between elevated plasma lipoproteins and a presumably normal endothelium using human veins in vivo; veins do not generally develop atherosclerosis and are appropriate for testing functional alterations.

Full dose-response curves were constructed in 13 hypercholesterolemic and 12 normocholesterolemic subjects by infusing bradykinin (0.25 to 508 ng/min) into hand veins preconstricted with the alpha-adrenergic agonist phenylephrine. The maximal relaxation induced by bradykinin was 80 +/- 38% in the controls and 103 +/- 40% in subjects with hypercholesterolemia (P = .08). Responsiveness to bradykinin was also determined after infusion of indomethacin (5.4 micrograms/min), a cyclooxygenase inhibitor, to block the contribution of prostaglandins; maximal responsiveness was greater in hypercholesterolemic subjects (112 +/- 41%) than in controls (81 +/- 31%) (P = .03). Hypercholesterolemic subjects were more sensitive to bradykinin, with an ED50 of 4.2 ng/min versus 10.9 ng/min in controls (P = .05); a similarly increased sensitivity was found in the presence of indomethacin. The response to a maximally effective dose of nitroglycerin was greater in hypercholesterolemic subjects (142 +/- 31%) versus 106 +/- 28% in controls (P = .007). In five hypercholesterolemic subjects, treated with lovastatin to normalize serum cholesterol concentrations, maximal responsiveness to bradykinin decreased from 103 +/- 52% to 80 +/- 28%.

These results demonstrate that hypercholesterolemia in humans does not impair endothelium-derived relaxing factor-mediated venodilation.